Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we report that membrane-active agents can reverse or circumvent multidrug resistance in tumor cells through alteration of membrane permeability. Two different cell lines are used to assay the drug-sensitivity: colchicine-resistant clone derived from human cancer KB cell line with multidrug resistance and P388 leukemia cells resistant to many anticancer agents such as adriamycin, vincristine and other agents. In the latter system, circumvention effect can be tested with mice bearing drug-sensitive or -resistant P388 leukemia in vivo. Thioridazine (calmodulin inhibitor), N-(p-methylbenzyl)decaprenylamine, N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine and amphotericin B (a sterol-binding polyene antibiotic) have been screened with these two drug-resistant cell systems. They overcome the multidrug resistance in Chr-24 as well as P388 leukemia cells resistant to adriamycin or vincristine. N-solanesyl-N,N'-bis(3,4-dimethoxylbenzyl)ethylenediamine can reverse the drug-resistance in vivo against mice bearing resistant leukemia. Mechanism to reverse the drug-resistance is to be discussed in relation with altered membrane permeability of the anticancer agents.
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PMID:Techniques to reverse or circumvent drug-resistance in vitro. 380 98

Thioridazine (TDZ), originally an anti-psychotic drug, suppresses several types of cancer and has specificity for leukemia stem cells. The present study was performed to assess its effect on lung cancer stem-like cells, as its effect remains unknown. TDZ was utilized to treat lung cancer stem-like cells (A549 sphere cells) and its cytotoxic effect and mechanism were evaluated in vitro and in vivo. TDZ elicited cytotoxicity in A549 sphere cells and inhibited their proliferation in a dose-dependent pattern. A549 sphere cells treated with TDZ showed nuclear fragmentation, increased G0/G1 phase distribution, positive Annexin V staining, and a change in the expression of caspase family and cell cycle-associated proteins. These results suggest the induction of caspase-dependent apoptosis and cell cycle arrest. In addition, TDZ treatment resulted in significant inhibitory effect on mice xenografts established by A549 sphere cells. TDZ repressed growth of lung cancer stem-like cells in vitro and in vivo, indicating its potential application in targeting lung cancer stem-like cells.
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PMID:Thioridazine has potent antitumor effects on lung cancer stem-like cells. 2845 91